Background: In elderly patients on chronic anticoagulation (i.e. warfarin and clopidogrel), falls have been shown to increase the incidence of intracranial hemorrhage (ICH) versus those not on anticoagulation (8.0% vs 5.3%). Mortality in those with ICH on anticoagulation is also higher than those who are not (21.9% vs 15.2%). Patients >65 years of age account for almost 10% of ED visits and 30% of admissions for traumatic brain injury. Even more frustrating is clinical decision rules on who to scan and not scan (i.e. Canadian CT Head Rule, New Orleans Criteria, and NEXUS-II criteria) do not apply to anticoagulated patients, because these patients were excluded in many of these studies. To date studies on patients taking warfarin who suffer minor head injuries have shown an incidence of ICH from 6.2 – 29%, suggesting that physicians should have a low threshold to scan these patients. Finally, several European guidelines suggest that all anticoagulated patients with head trauma should be admitted for observation, even if the initial head CT is negative, based on limited data. Unfortunately, the risk of traumatic intracranial hemorrhage after blunt head trauma for patients on warfarin and clopidogrel, has never really been studied in a large generalizable cohort or under a rigorous, prospective, multicenter designed studies. Therefore, knowledge of the true prevalence and incidence of immediate and delayed traumatic ICH in patients on anticoagulation would allow for evidence based decisions to be made about initial patient evaluation and disposition instead of admitting all patients for observation for concern of delayed ICH [1].

Neurosurgical Intervention = Use of intracranial pressure monitor or brain tissue oxygen probe, placement of a burr hole, craniotomy/craniectomy, intraventricular catheter or subdural drain, or the use of mannitol or hypertonic saline

Outcomes:

Prevalence of immediate and delayed ICH in anticoagulated (warfarin and clopidogrel) patients with minor head injury

Majority of patients had a GCS of 15 at time of examination (n = 932; 87.6%)

In patients receiving warfarin 603/768 (78.5%) had an INR drawn on initial evaluation with median level of 2.5

95.5% had INR ≥1.3

76.0% had INR ≥2.0

1000/1064 patients (94.0%) had an initial head CT during initial evaluation

70/1000 patients had immediate traumatic ICH

33/276 (12%) of pts on clopidogrel (95% CI 8.4 – 16.4%)

37/724 (5.1%) of pts on warfarin (95% CI 3.6 – 7.0%)

45/70 (64.3%) had a normal mental status (GCS = 15)

10/70 (14.2%) had no loss of consciousness, a normal mental status, and no evidence of trauma above the clavicles

Delayed traumatic ICH was assessed in 930 patients with an initial normal head CT

4/687 (0.6%) patients had delayed ICH on warfarin

0/243 (0%) patients had delayed ICH on clopidogrel

2/4 patients with traumatic ICH died (None of the 4 had neurosurgical interventions)

Strengths:

This study identifies the prevalence of traumatic ICH in a more generalizable population because the majority of the patients were patients seen in community EDs and not just trauma registries

This study alone, roughly doubles the number of previously studied CT results for head-injured patients receiving warfarin and quadruples the number of such patients investigated for delayed hemorrhages [2].

Limitations:

This was an observational study, meaning not all patients got initial CT scans and therefore some patients may have had an undiagnosed traumatic ICH, even though none were identified on patient follow up

Increased immediate traumatic ICH in the clopidogrel group may be due to the higher prevalence of concomitant aspirin use compared with the warfarin group (8.1% vs 2.5%)
Data was not collected on patients with isolated preinjury aspirin use or patients without preinjury antiplatelet or anticoagulation use

Patients on warfarin may be more acutely aware of bleeding risks associated with their medication than patients on clopidogrel. This could mean that more patients on warfarin are apt to seek emergency care, than patients on clopidogrel, diluting the warfarin pool and hence underestimating initial traumatic ICH in the warfarin group and overestimating initial traumatic ICH in the clopidogrel group

Patients on New Oral Anticoagulants (NOACs) were not reviewed in this trial therefore making it difficult to make any comments or recommendations of patients on these agents.

Discussion:

Although this was an observational study, it is safe to say that in this large and generalizable cohort of patients receiving warfarin or clopidogrel that the development of a delayed traumatic ICH after an initial negative head CT is rare and does not warrant routine hospitalization for observation or immediate anticoagulation reversal

The authors of this paper found 10 studies of patients on preinjury warfarin and 3 studies of patients on preinjury clopidogrel that reported prevalence of immediate traumatic intracranial hemorrhage.

The overall quality of these studies were very limited due to the majority being small (<100 patients), retrospective registry studies, and the fact that these studies suffered from inclusion bias because sampled populations were from trauma registries while excluding patients not evaluated by trauma services

The prevalence of traumatic ICH is most likely falsely elevated in these studies due to the inclusion of patients transferred to trauma centers, meaning these were patients with other traumatic injuries and a worse mechanism of injury than just a simple fall from standing
It is pretty concerning how high the prevalence of immediate traumatic ICH is in well-appearing patients

>60% of patients with a normal mental status (GCS = 15)

11% in the warfarin group and 18% in the clopidogrel group had no loss of consciousness, a normal mental status, and no physical evidence of trauma above the clavicles

The authors of this paper also state that a survey of clinical practices among North American trauma surgeons indicated that 74% of them would reverse patients receiving warfarin who have blunt head trauma despite a normal initial head CT and 66% would use fresh frozen plasma.

Author Conclusion: Although there may be unmeasured confounders that limit intergroup comparison, patients on clopidogrel have a higher prevalence of immediate traumatic ICH compared to patients on warfarin. Delayed traumatic ICH is rare and only occurred on patients taking warfarin. Discharging patients receiving anticoagulant or antiplatelet medications from the ED after a normal initial head CT is reasonable, but appropriate instructions are required because delayed traumatic ICH may still occur.

Clinical Take Home Points:

Routine head CT in head-injured patients with previous warfarin or clopidogrel use should be performed, even in well-appearing patients regardless of lack of clinical findings

Delayed traumatic ICH in patients on therapeutic warfarin and clopidogrel is very rare and these patients may be discharged home after a negative initial head CT, but with explicit discharge instructions and close follow up.

24 hour observation of patients with poor functional capacity, long travel times to get to a hospital, and/or patients with no one at home to watch them would also be an acceptable alternative

Patients with therapeutic anticoagulation, blunt head trauma, and a negative initial head CT DO NOT need to have their anticoagulation aggressively reversed

Patients with supratherapeutic anticoagulation, blunt head trauma, and a negative initial head CT were not explicitly discussed in this paper, but in my practice, I would have a low threshold to admit them for frequent neuro checks, repeat measurement of INR (while holding anticoagulation), and possibly repeat head CT if any change in exam

Related Posts

Salim,
Any commonalities of clinical course in the 4 delayed bleeders? Worked in a “overnight Obs/repeat head CT” place, now in more of a “family will watch them” place. Would be interested to know any clinical commonalities in the delayed bleeders

Hello Clint,
Great question. Not sure how helpful the commonalities will be, but all the patients:
1. Were 63 years of age and older
2. Had a ground level fall, isolated head injury
3. Had an initial GCS of 15
4. Had initial INR of <2.0, with the exception of one 4.95

I didn't really find a useful theme in all this, except that older patients (Age >60 – 65), with no findings on exam, still warrant an initial head CT regardless of initial neuro status. Curious if you have noticed any themes where you work.

Great piece Sal. I was surprised that the two groups of INR>1.4 and >2 fared similar ICH rates of 6.3% and 7%. I’d still like to know what the peak of the risk curve is in the coumadin group for delayed bleed. They divided up into INR >1.4 and >2 group but what about >3? >4?>5? The delayed bleeders in this study were all >60 but 3/4 had INR<2! Still the numbers of delayed bleed overall lower than some studies and with more powerful overall study numbers. I'm still not sure we have decisive data on who to keep for observation and rescan? Probably the older and higher INR? That's only my opinion without good supporting data.

Hey Scott,
Agree with your comments and in the conclusions we state, not sure what to do with the patients with INRs that are supratherapeutic. Currently I am admitting them for observation stay and neuro checks, not necessarily scans, unless neurological or mental status changes. Also if patients don’t have good follow up, long travel times to get to closest ED, live by themselves, or no one to do 24 hour observation I also tend to admit. As for the better powered studies, these were studies from trauma registries, so a lot more polytrauma, and in some cases patients not seen by trauma not put in registries, therefore they may overestimate risk of delayed ICH. Unfortunately, this is the best evidence we have, in a general non-trauma registry population,so far, but lots more questions than answers in my opinion:

1. As you stated at what INR is risk increased?
2. At what INR do we need to reverse anticoagulation?
2. What do we do with patients on NOACs?